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Purpose: Hydroxychloroquine (HCQ) can cause irreversible damage to the retina, especially when taken over longer periods. The American Academy of Ophthalmology recommends a regimen for dosing, screening, and monitoring of patients treated with HCQ. We present an unusual case of a rapid development of severe HCQ-associated retinopathy already after 2 years after commencing HCQ treatment., Methods: Observational case report. Clinical examination, optical coherence tomography, fundus autofluorescence imaging, perimetry, and full-field and multifocal electroretinography were performed. Ancillary tests included neoplastic and paraneoplastic work-up, vitamin levels, and whole-exome sequencing, to rule out other potential causes of a panretinal degeneration., Results: We report on a 58-year-old woman with rheumatoid arthritis, treated initially with 200 mg HCQ daily for 1 year (daily dose 3.6 mg/kg), then 400 mg daily for 1 year (daily dose 7.2 mg/kg), and a cumulative dose of 216 g. Her medical history was otherwise unremarkable. No family history for inherited retinal conditions. She was referred due to a rapid and sudden progressive and severe concentric visual field constriction, 2 years after commencing HCQ treatment., Conclusion: This case of a rapid-onset, severe panretinal degeneration shortly after start of HCQ treatment suggests underlying mechanisms and risk factors for HCQ toxicity in addition to those previously reported and a potential need for supplementary screening tests to prevent HCQ toxicity. American Academy of Ophthalmology dosing guidelines of 5 mg/kg should be strictly adhered to in patients receiving HCQ therapy., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)